Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.     

Inhibition of platelet phosphatidylinositol synthetase by an analog of CDP-diacylglycerol

Unpublished portions of the synthesis of a phosphinate-phosphonate diether analog of CDPdiacylglycerol are reported. The liponucleotide analog was found to be a very powerful inhibitor of platelet PI synthetase; kinetic data suggest a competitive inhibition mechanism. The structural specificity of CDPdiacylglycerol for liponucleotide-mediated biosynthetic reactions is discussed.     

An iso-random Bi Bi mechanism for adenylate kinase.

An iso-random Bi Bi mechanism has been proposed for adenylate kinase. In this mechanism, one of the enzyme forms can bind the substrates MgATP and AMP, whereas the other form can bind the products MgADP and ADP. In a catalytic cycle, the conformational changes of the free enzyme and the ternary complexes are the rate-limiting steps. The AP(5)A inhibition equations derived from this mechanism show theoretically that AP(5)A acts as a competitive inhibitor for the forward reaction and a mixed noncompetitive inhibitor for the backward reaction.     

Electrophysiologic effects of serotonin on atrioventricular conduction in dogs

In 12 anaesthetized dogs acute effects of serotonin on the atrioventricular conduction system were studied by obtaining intracardiac electrograms. The significant increase in the heart rate and decrease in aortic pressure elicited by an intravenous infusion of 50 mg/kg.min serotonin for 30 minutes were comparable to those observed in previous investigations. Our data indicate a serotonin induced acceleration of the sinus node pacemaker and atrioventricular conduction by direct and indirect mechanisms.     

NMR studies of the conformational change in human N-p21ras produced by replacement of bound GDP with the GTP analog GTP gamma S.

1H-Detected 15N-edited NMR in solution was used to study the conformational differences between the GDP- and GTP gamma S-bound forms of human N-p21ras. The amide protons of 15N-labeled glycine and isoleucine were observed. Resonances were assigned to residues of particular interest, glycines-60 and -75 and isoleucines-21 and -36, by incorporating various 13C-labeled amino acids in addition to [15N]glycine and [15N]iosleucine and by replacing Mg2+ by Co2+. When GTP gamma S replaced GDP in the active site of p21ras, only 5 of the 14 glycine amide resonances show major shifts, indicating that the conformational effects are fairly localized. Responsive glycines-10, -12, -13, and -15 are in the active site. Gly-75, located at the far end of a conformationally-active loop and helix, also responds to substitution of GTP gamma S for GDP, while Gly-77 does not, supporting a role for Gly-75 as a swivel point for the conformational change. The amide proton resonances of isoleucines-36 and -21 and a third unidentified isoleucine also undergo major shifts upon replacement of GDP by GTP gamma S. Thus, the effector-binding loop containing Ile-36 is confirmed to be involved in the conformational change, and the alpha-helix containing Ile-21 is also shown to be affected.     

Comparative analysis of the HBsAg level in human blood preparations

A total of 218 batches of blood preparations produced from different raw materials have been studied by means of enzyme immunoassay kits (Abbott Laboratories, USA). The assays have revealed that the preparations under study are nonstandard with respect to the content and isolation rate of HBsAg, the marker of hepatitis B virus. These data necessitate search for the ways of improving the quality of blood preparations.     

Molecular basis of biodegradation of chloroaromatic compounds

Chlorinated aromatic hydrocarbons are widely used in industry and agriculture, and comprise the bulk of environmental pollutants. Although simple aromatic compounds are biodegradable by a variety of degradative pathways, their halogenated counterparts are more resistant to bacterial attack and often necessitate evolution of novel pathways. An understanding of such evolutionary processes is essential for developing genetically improved strains capable of mineralizing highly chlorinated compounds. This article provides an overview of the genetic aspects of dissimilation of chloroaromatic compounds and discusses the potential of gene manipulation to promote enhanced evolution of the degradative pathways.